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Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2

Khan, MF; Spurgeon, S; Von der Haar, T; (2018) Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2. Journal of Theoretical Biology , 445 pp. 92-102. 10.1016/j.jtbi.2018.02.020. Green open access

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Abstract

Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2.

Type: Article
Title: Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jtbi.2018.02.020
Publisher version: http://dx.doi.org/10.1016/j.jtbi.2018.02.020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Protein synthesis; Translation; Translational control; eIF2; eIF2B; Gcn2; Control engineering; Robustness
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Electronic and Electrical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10046390
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